To clarify the mechanisms of colon malignancy, each genetic event lying behind the progression of colon tumors must be identified. There has been great interest in developing culture systems of colonic epithelial cells, since such systems are invaluable to the study of intestinal cell differentiation, as well as tumor etiology. Biochemical and morphological differentiation can be induced in HT29 colon carcinoma cells by many types of agents and by changing the nutrient conditions. We have established permanently-differentiated subclones from sodium butyrate-treated HT29 colon carcinoma cells. However, the mechanisms underlying these phenotypical changes remain to be elucidated. Previous karyotypic analysis indicated that, in these subclones, chromosomes 10q, 14q and 16q were decreased. This time, we molecularly confirmed that the number of chromosome band 10q was reduced in three differentiated HT29 cells. These results suggest that the gene(s) which suppresses differentiation programs may be located on chromosome 10q in HT29 cells. Besides this cytogenetic approach, we have attempted to identify genes which may be important for colon cell differentiation and colon tumor development. A unique cDNA (cori-1) was isolated from a tumor-enriched cDNA library derived from human colon tumor tissue. It is preferentially expressed in HT29 cells rather than in the sodium butyrate-induced differentiated subclone, and has a unique characteristic encoding an antisense strand of a 5' untranslated region of anti-oncogene, krev-1, mRNA. We have also isolated mouse cori-1 cDNA. By comparing human and mouse sequences, we determined a possible open reading frame. Finally, we found that the induced expression of cori-1 mRNA can enhance the function of the krev-1 gene by suppressing colony formation of transformed mouse fibroblasts. These results suggest a unique mechanism of the regulation of krev expression performed by cori-1 transcripts.